There's essentially no data to speak to this question. I would say that most cancer experts are wary about supplements that tend to have no evidence of a benefit and the potential for detrimental interactions. However, there's also essentially no evidence to demonstrate harm either. It's largely that oncologists tend to be more likely to presume that a treatment is not beneficial and potentially harmful, while people who are in the supplement business or favor complementary medicine largely operate under a presumption that supplements that are untested are going to be helpful.
Dr. West~ thank you for your explanation of why supplements are so controversy which makes it very difficult for the patient who has been diagnosed with a stage IV disease. Our feeling that the need for adjunctive therapy (supplements) is necessary to fight this disease and that chemo/target drug will not do it alone (just our opinion) so we are very conflicted as to our decision in using supplements. That being said, I do have a couple other questions:
1) Why does Tarceva become resistant in some patients?
2) Is there any documentation on the percentage of patients who have become resistant to Tarceva?
3) How many months did it take for the Tarceva to become resistant?
4) Can oncologists determine if Tarceva will become resistant by looking at the patient's mutation, overall health, age, if it's a fast spreading cancer, etc. even before the patient starts Tarceva?
3) I have read the article "The HDAC inhibitor, MPT0E028, enhances erlotinib-induced cell death in EGFR-TKI-resistant NSCLC cells". Has MPT0E028 become available yet or is it just in the early stages?
4) Also, as noted above, my husband tested + EGFR Leu858Arg mutation ~ what is Leu858Arg?
Hi kcarn, Welcome to Grace! I'm very sorry your husband is dx with stage IV nsclc.
You've asked a lot of good questions. Most of which have been covered many times before or can be searched easily enough. As per our guidelines, You may want to do a search for some of the key terms in your question to see whether you can get the answer without asking it again.
Because we’re trying to offer assistance to many people, we ask that people not provide a long list of questions. We can’t spend 30 minutes answering a post with 8 exhaustive questions. Better to prioritize one or two and come back with additional questions over time. We need to take turns here.
A Grace search didn't come up with any results for Leu858Argn but a google search found this, "Classic EGFR activating mutations, such as inframe deletions in exon 19 or the Leu858Arg (L858R) point mutation in exon 21 are associated with sensitivity to first generation quinazoline reversible EGFR tyrosine kinase inhibitors (TKIs)". http://www.ncbi.nlm.nih.gov/pubmed/21764376
It's more technical than we usually get but it means that your husband is very likely to have a good response to tarceva.
All people become resistant to tarceva at some point. Some as quickly as a few months and some only after 3 or 4 years. Resistance too can be a tricky term to define. Dr. West has shared his algorithm for planning after resistance has begun in this post, http://cancergrace.org/lung/2013/01/23/acquired-resistance-algorithm/ht…
Thank you, Janine. I do have two questions (I promise it won't be long). My husband had pain in his spine back in May and was being evaluated. He had no other side effects whatsoever (maybe a very slight cough). The official diagnosis of lung cancer with mets to the spine came about in Sept. He was treated with 10 days of radiation and given 1 treatment of carb/alimta and at that time was awaiting biopsy results. After treatments he had a bout of radiation enteritis and had delayed the treatment of tarceva. The oncologist will be getting baseline CT before starting tarceva. Here's my questions:
1) Being that it has been since May and he has had no side-effects whatsoever, no cough, pulse ox 100%, etc. does this mean this could be a slow moving cancer?
2) Is it likely that there may be shrinkage from 1 treatment of carb/alimta?
It's certainly possible to have slow-growing cancer. and the best way to know that is to check two main things:
1) has the person been experiencing a clinical decline and worsening symptoms at a relatively fast pace or minimally (even not at all) over time prior to treatment? Someone losing weight or experiencing worsening shortness of breath over 2-3 months between initial symptoms and diagnosis/treatment is likely to have a rapidly progressing cancer. On the other hand, someone diagnosed with minimally symptoms and who continues to do and feel the same for months before treatment likely has indolent disease.
2) Was there any meaningful interval between the first imaging done and one or more later imaging studies done before treatment started, such as 3-4 weeks (or longer) between a first chest CT and a later PET/CT? In that time, was there significant progression or just a few millimeters of growth, or less?
This is a big enough variable that I wrote a post about it as a critical variable:
The Leu858Arg mutation is the common L858R, exon 21 mutation that is one of the 2 common activating EGFR mutations.
Unfortunately, just about everyone with an activating mutation develops acquired resistance, with a median duration of response of 10-13 months or so, but with some patients responding into the range of years. There is no way to predict which patients will progress sooner or later.
I'm not aware of any work being done with MPT0E028.
It is possible to have response after just one treatment it just depends as Dr. West said. When I said "side effects" I'm talking about the what happens to the body because of treatment but aside from killing the cancer. Symptoms are the effects cancer has on the body, side effects are the effects treatment has on the body. With tarceva there are fairly predictable side effects including skin drying out. The posts on side effects are what can be done to mitigate the bad effects tarceva has. It will become clear once you move forward.
I'm going to guess that he has a slow-growing cancer because he had not declined or has had worsening symptoms. His scans have not showed a significant progression; although, on last scan there were 2 small nodules seen, but I'm not in the healthcare profession so I can only go on speculation. We'll see what the CAT scan shows on Friday. However, he's been the sickest since radiation and chemo being hospitalized for a week, lost significant weight, and now he has flu-like symptoms!!! He's supposed to gain weight before his next visit with his oncologist so we can start tarceva.
What are the pros and cons to tarceva vs continuing on carb/alimta vs. do nothing and just watch and wait???
After completion of 4-6 cycles of first line chemo for advanced NSCLC, there is an option, though certainly not a mandate, of doing maintenance therapy until progression of disease.
The advantages of either switching to Tarceva or continuing on Alimta if no progression are that either one is associated with a longer time before the cancer progresses. There isn't a direct comparison of one versus another, and the numbers in terms of duration of time until progression are reasonably comparable for the different studies with one or another, with a bit of an advantage to Alimta. We don't continue the carboplatin after more than about 6 cycles typically, and it's very common and reasonable to stop after 4 cycles, since you tend to reach a point of diminishing returns in terms of side effects vs. benefit of the doublet vs. single agent treatment after 4-6 cycles of chemo.
Presuming starting on chemo, an advantage of continuing on one of the same chemo agents started earlier (Alimta, specifically) is that you maximize the benefit of current treatment before moving on to the next one -- you don't leave any of that potential efficacy behind. And it's often well tolerated, though it is an every 3 week IV infusion.
Switching to Tarceva provides an oral alternative that isn't standard chemo, so patients can be on active anti-cancer treatment but not be tethered to IV therapy, not have ongoing side effects of chemo, etc. And it ensures that all patients will get access to Tarceva at some point, which is very helpful for a minority of patients and modestly helpful for a broader range of patients.
Taking a break is still profoundly reasonable. There is no evidence that people don't do just as well getting the same drugs later vs. earlier, and one major impetus for maintenance therapy is that companies push it to ensure that their drug gets used. But a treatment break is a fine choice that many experts (including this one) favor for selected patients.
1) If he chooses to go on Tarceva and for whatever reason does not work out (i.e. side-effects, becomes resistant, etc.) can he go back to carb/alimta?
Also, MRI of brain was done in the beginning of the diagnosis phase, a couple small lesions (2-3 mm) mets were found which the radiologist definitely mentioned were mets; however, doctors thought they were too small to really say they were mets, that they could be blood vessels, etc. and to not worry.
2) Would Tarceva hit those brain lesions?
3. Also will be going on xgeva (?? SP) for bones ~ does that also act as a cancer treatment?
If I have it correct that he only had one treatment of carbo/alimta, then it would be perfectly reasonable to return to it after trying Tarceva. After just one treatment it would be hard to know if it is going to work for him, so it's certainly a good option.
There is some evidence that Tarceva can cross the blood-brain barrier and treat brain lesions, although radiation is the most effective and best favored treatment. But since there is some doubt whether these are mets and they are small and asymptomatic, treatment with Tarceva and continued surveillance is reasonable.
I have little to add to Jim's thoughtful answers, except to note that XGEVA (denosumab) is primarily given as a treatment to reduce the risk of future skeletal complications (need for radiation for bone metastases, need for opioid pain medication for bone metastases, and/or fracture from structural instability caused by bone metastasis); there is a potential improvement in survival that hasn't been as clearly defined.
So my husband did get the results of his CAT scan of his chest and it showed 1/3 shrinkage of the tumor, pulmonary nodules are gone, no evidence of any new pulmonary lung nodules, and also had shrinkage of lymph nodes. Do you think this is a substantial shrinkage after just one chemo treatment? I think it is but what do I know. (BTW: he is to start Tarceva tomorrow).
Congratulations! It's a very nice response, especially early into treatment. I think the key question is why you'd necessarily start Tarceva when you have early feedback that the current treatment is doing well. If we know someone is responding well to one treatment, we don't necessarily want to use a second potentially effective agent concurrently, tending to favor a sequential approach instead.
Dr. West~ just to comment... it was decided early on to start Tarceva once the second biopsy came back, but that the doctor wanted to get something started as treatment was delayed so started with carbo/alimta, and since he does have possible brain mets, I think the thinking would be Tarceva could possibly reach those. He did have radiation/chemo back-to-back and had complications from the radiation (hospitalized for a week with radiation enteritis), lost a lot of weight and very weak so I guess the doctor felt Tarceva would be better tolerated at this time. He feels so much better now and has gained back a lot of his weight. Do you know how long it takes for side-effects to appear from the Tarceva???
It's very reasonable to change treatments when one isn't being tolerated very well. I hope tarceva is easier on your husband. It will certainly be different.
Side effects from tarceva are variable including their onset. Some people develop some of them as soon as starting the drug and usually include very dry skin problems. From what everyone who's taken the drug or cared for some who takes the drug it's recommended to start a moisturizing regime when or even before you start the treatment. Something clean and basic without any extra ingredients. Also diarrhea is an issue for some so having a drug like imodium handy from the beginning is an excellent idea.
There's literally pages and pages written like on the subject and a look through the EGFR forums will help give a good understanding of what to expect. http://cancergrace.org/forum/cancer-treatments-symptom-management/egfr-… I don't want to excuse your question by any means I just don't want Dr. West to need to repeat what's been said. I hope you understand that we want to use his time as judiciously as possible.
By all means if you don't find what you're looking for just ask,
Janine
forum moderator
Most of the side effects with Tarceva emerge within 2-3 weeks of starting the drug. That's when the rash and diarrhea tend to be worst, and things often seem to improve a bit gradually after that. There are some chronic side effects, like nail infections and cracks in the fingertips, which tend to be more problematic with very long-term use, but most people on EGFR inhibitors for long enough to experience these issues are benefiting so much from them that they are very inclined to continue on them over time.
Reply # - November 22, 2013, 10:12 PM
Reply To: ADDING SUPPLEMENTS TO TARCEVA REGIMEN
There's essentially no data to speak to this question. I would say that most cancer experts are wary about supplements that tend to have no evidence of a benefit and the potential for detrimental interactions. However, there's also essentially no evidence to demonstrate harm either. It's largely that oncologists tend to be more likely to presume that a treatment is not beneficial and potentially harmful, while people who are in the supplement business or favor complementary medicine largely operate under a presumption that supplements that are untested are going to be helpful.
-Dr. West
Reply # - November 23, 2013, 08:14 AM
Reply To: ADDING SUPPLEMENTS TO TARCEVA REGIMEN
Dr. West~ thank you for your explanation of why supplements are so controversy which makes it very difficult for the patient who has been diagnosed with a stage IV disease. Our feeling that the need for adjunctive therapy (supplements) is necessary to fight this disease and that chemo/target drug will not do it alone (just our opinion) so we are very conflicted as to our decision in using supplements. That being said, I do have a couple other questions:
1) Why does Tarceva become resistant in some patients?
2) Is there any documentation on the percentage of patients who have become resistant to Tarceva?
3) How many months did it take for the Tarceva to become resistant?
4) Can oncologists determine if Tarceva will become resistant by looking at the patient's mutation, overall health, age, if it's a fast spreading cancer, etc. even before the patient starts Tarceva?
3) I have read the article "The HDAC inhibitor, MPT0E028, enhances erlotinib-induced cell death in EGFR-TKI-resistant NSCLC cells". Has MPT0E028 become available yet or is it just in the early stages?
4) Also, as noted above, my husband tested + EGFR Leu858Arg mutation ~ what is Leu858Arg?
Reply # - November 23, 2013, 12:01 PM
Reply To: ADDING SUPPLEMENTS TO TARCEVA REGIMEN
Hi kcarn, Welcome to Grace! I'm very sorry your husband is dx with stage IV nsclc.
You've asked a lot of good questions. Most of which have been covered many times before or can be searched easily enough. As per our guidelines, You may want to do a search for some of the key terms in your question to see whether you can get the answer without asking it again.
Because we’re trying to offer assistance to many people, we ask that people not provide a long list of questions. We can’t spend 30 minutes answering a post with 8 exhaustive questions. Better to prioritize one or two and come back with additional questions over time. We need to take turns here.
A Grace search didn't come up with any results for Leu858Argn but a google search found this, "Classic EGFR activating mutations, such as inframe deletions in exon 19 or the Leu858Arg (L858R) point mutation in exon 21 are associated with sensitivity to first generation quinazoline reversible EGFR tyrosine kinase inhibitors (TKIs)". http://www.ncbi.nlm.nih.gov/pubmed/21764376
It's more technical than we usually get but it means that your husband is very likely to have a good response to tarceva.
All people become resistant to tarceva at some point. Some as quickly as a few months and some only after 3 or 4 years. Resistance too can be a tricky term to define. Dr. West has shared his algorithm for planning after resistance has begun in this post, http://cancergrace.org/lung/2013/01/23/acquired-resistance-algorithm/ht…
There is much written on the subject of EGFR and TKIs, http://cancergrace.org/lung/?cat=26
Getting a jump on how to head off side effects from tarceva may be a better place to start. http://cancergrace.org/cancer-treatments/files/2011/09/qa-dr-lacouture-…
I hope this helps to get you started,
Janine
Reply # - November 23, 2013, 12:03 PM
Reply To: ADDING SUPPLEMENTS TO TARCEVA REGIMEN
I ran out of room but I wanted to share this with you too in case you're not familiar with how forums work. We have a forum just for EGFR inhibitors and can be found here, http://cancergrace.org/forum/cancer-treatments-symptom-management/egfr-…
Reply # - November 23, 2013, 02:46 PM
Reply To: ADDING SUPPLEMENTS TO TARCEVA REGIMEN
Thank you, Janine. I do have two questions (I promise it won't be long). My husband had pain in his spine back in May and was being evaluated. He had no other side effects whatsoever (maybe a very slight cough). The official diagnosis of lung cancer with mets to the spine came about in Sept. He was treated with 10 days of radiation and given 1 treatment of carb/alimta and at that time was awaiting biopsy results. After treatments he had a bout of radiation enteritis and had delayed the treatment of tarceva. The oncologist will be getting baseline CT before starting tarceva. Here's my questions:
1) Being that it has been since May and he has had no side-effects whatsoever, no cough, pulse ox 100%, etc. does this mean this could be a slow moving cancer?
2) Is it likely that there may be shrinkage from 1 treatment of carb/alimta?
Thank you!
Reply # - November 23, 2013, 05:14 PM
Reply To: ADDING SUPPLEMENTS TO TARCEVA REGIMEN
It's certainly possible to have slow-growing cancer. and the best way to know that is to check two main things:
1) has the person been experiencing a clinical decline and worsening symptoms at a relatively fast pace or minimally (even not at all) over time prior to treatment? Someone losing weight or experiencing worsening shortness of breath over 2-3 months between initial symptoms and diagnosis/treatment is likely to have a rapidly progressing cancer. On the other hand, someone diagnosed with minimally symptoms and who continues to do and feel the same for months before treatment likely has indolent disease.
2) Was there any meaningful interval between the first imaging done and one or more later imaging studies done before treatment started, such as 3-4 weeks (or longer) between a first chest CT and a later PET/CT? In that time, was there significant progression or just a few millimeters of growth, or less?
This is a big enough variable that I wrote a post about it as a critical variable:
http://cancergrace.org/cancer-101/2013/01/16/progression-rate/
In terms of your other questions, there is a lot written about acquired resistance, most covered here or in the links on that page:
http://cancergrace.org/lung/2012/08/05/acquired-resistance-faq/
The Leu858Arg mutation is the common L858R, exon 21 mutation that is one of the 2 common activating EGFR mutations.
Unfortunately, just about everyone with an activating mutation develops acquired resistance, with a median duration of response of 10-13 months or so, but with some patients responding into the range of years. There is no way to predict which patients will progress sooner or later.
I'm not aware of any work being done with MPT0E028.
-Dr. West
Reply # - November 23, 2013, 05:48 PM
Reply To: ADDING SUPPLEMENTS TO TARCEVA REGIMEN
It is possible to have response after just one treatment it just depends as Dr. West said. When I said "side effects" I'm talking about the what happens to the body because of treatment but aside from killing the cancer. Symptoms are the effects cancer has on the body, side effects are the effects treatment has on the body. With tarceva there are fairly predictable side effects including skin drying out. The posts on side effects are what can be done to mitigate the bad effects tarceva has. It will become clear once you move forward.
All best,
Janine
Reply # - November 25, 2013, 04:26 PM
Reply To: ADDING SUPPLEMENTS TO TARCEVA REGIMEN
I'm going to guess that he has a slow-growing cancer because he had not declined or has had worsening symptoms. His scans have not showed a significant progression; although, on last scan there were 2 small nodules seen, but I'm not in the healthcare profession so I can only go on speculation. We'll see what the CAT scan shows on Friday. However, he's been the sickest since radiation and chemo being hospitalized for a week, lost significant weight, and now he has flu-like symptoms!!! He's supposed to gain weight before his next visit with his oncologist so we can start tarceva.
What are the pros and cons to tarceva vs continuing on carb/alimta vs. do nothing and just watch and wait???
Reply # - November 25, 2013, 07:53 PM
Reply To: ADDING SUPPLEMENTS TO TARCEVA REGIMEN
After completion of 4-6 cycles of first line chemo for advanced NSCLC, there is an option, though certainly not a mandate, of doing maintenance therapy until progression of disease.
The advantages of either switching to Tarceva or continuing on Alimta if no progression are that either one is associated with a longer time before the cancer progresses. There isn't a direct comparison of one versus another, and the numbers in terms of duration of time until progression are reasonably comparable for the different studies with one or another, with a bit of an advantage to Alimta. We don't continue the carboplatin after more than about 6 cycles typically, and it's very common and reasonable to stop after 4 cycles, since you tend to reach a point of diminishing returns in terms of side effects vs. benefit of the doublet vs. single agent treatment after 4-6 cycles of chemo.
Presuming starting on chemo, an advantage of continuing on one of the same chemo agents started earlier (Alimta, specifically) is that you maximize the benefit of current treatment before moving on to the next one -- you don't leave any of that potential efficacy behind. And it's often well tolerated, though it is an every 3 week IV infusion.
Switching to Tarceva provides an oral alternative that isn't standard chemo, so patients can be on active anti-cancer treatment but not be tethered to IV therapy, not have ongoing side effects of chemo, etc. And it ensures that all patients will get access to Tarceva at some point, which is very helpful for a minority of patients and modestly helpful for a broader range of patients.
Taking a break is still profoundly reasonable. There is no evidence that people don't do just as well getting the same drugs later vs. earlier, and one major impetus for maintenance therapy is that companies push it to ensure that their drug gets used. But a treatment break is a fine choice that many experts (including this one) favor for selected patients.
Good luck.
-Dr. West
Reply # - November 25, 2013, 08:18 PM
Reply To: ADDING SUPPLEMENTS TO TARCEVA REGIMEN
1) If he chooses to go on Tarceva and for whatever reason does not work out (i.e. side-effects, becomes resistant, etc.) can he go back to carb/alimta?
Also, MRI of brain was done in the beginning of the diagnosis phase, a couple small lesions (2-3 mm) mets were found which the radiologist definitely mentioned were mets; however, doctors thought they were too small to really say they were mets, that they could be blood vessels, etc. and to not worry.
2) Would Tarceva hit those brain lesions?
3. Also will be going on xgeva (?? SP) for bones ~ does that also act as a cancer treatment?
Reply # - November 26, 2013, 05:09 AM
Reply To: ADDING SUPPLEMENTS TO TARCEVA REGIMEN
Hi kcarn,
If I have it correct that he only had one treatment of carbo/alimta, then it would be perfectly reasonable to return to it after trying Tarceva. After just one treatment it would be hard to know if it is going to work for him, so it's certainly a good option.
There is some evidence that Tarceva can cross the blood-brain barrier and treat brain lesions, although radiation is the most effective and best favored treatment. But since there is some doubt whether these are mets and they are small and asymptomatic, treatment with Tarceva and continued surveillance is reasonable.
There is some evidence that Xgeva provides a survival benefit: http://cancergrace.org/lung/2011/07/15/xgevavszometascagliottiwclc/
Good luck with Tarceva!
JimC
Forum moderator
Reply # - November 26, 2013, 08:43 PM
Reply To: ADDING SUPPLEMENTS TO TARCEVA REGIMEN
I have little to add to Jim's thoughtful answers, except to note that XGEVA (denosumab) is primarily given as a treatment to reduce the risk of future skeletal complications (need for radiation for bone metastases, need for opioid pain medication for bone metastases, and/or fracture from structural instability caused by bone metastasis); there is a potential improvement in survival that hasn't been as clearly defined.
-Dr. West
Reply # - December 2, 2013, 08:51 PM
Reply To: ADDING SUPPLEMENTS TO TARCEVA REGIMEN
So my husband did get the results of his CAT scan of his chest and it showed 1/3 shrinkage of the tumor, pulmonary nodules are gone, no evidence of any new pulmonary lung nodules, and also had shrinkage of lymph nodes. Do you think this is a substantial shrinkage after just one chemo treatment? I think it is but what do I know. (BTW: he is to start Tarceva tomorrow).
Reply # - December 3, 2013, 06:38 AM
Reply To: ADDING SUPPLEMENTS TO TARCEVA REGIMEN
Congratulations! It's a very nice response, especially early into treatment. I think the key question is why you'd necessarily start Tarceva when you have early feedback that the current treatment is doing well. If we know someone is responding well to one treatment, we don't necessarily want to use a second potentially effective agent concurrently, tending to favor a sequential approach instead.
-Dr. West
Reply # - December 5, 2013, 03:02 AM
Reply To: ADDING SUPPLEMENTS TO TARCEVA REGIMEN
Dr. West~ just to comment... it was decided early on to start Tarceva once the second biopsy came back, but that the doctor wanted to get something started as treatment was delayed so started with carbo/alimta, and since he does have possible brain mets, I think the thinking would be Tarceva could possibly reach those. He did have radiation/chemo back-to-back and had complications from the radiation (hospitalized for a week with radiation enteritis), lost a lot of weight and very weak so I guess the doctor felt Tarceva would be better tolerated at this time. He feels so much better now and has gained back a lot of his weight. Do you know how long it takes for side-effects to appear from the Tarceva???
Reply # - December 5, 2013, 06:11 AM
Reply To: ADDING SUPPLEMENTS TO TARCEVA REGIMEN
It's very reasonable to change treatments when one isn't being tolerated very well. I hope tarceva is easier on your husband. It will certainly be different.
Side effects from tarceva are variable including their onset. Some people develop some of them as soon as starting the drug and usually include very dry skin problems. From what everyone who's taken the drug or cared for some who takes the drug it's recommended to start a moisturizing regime when or even before you start the treatment. Something clean and basic without any extra ingredients. Also diarrhea is an issue for some so having a drug like imodium handy from the beginning is an excellent idea.
There's literally pages and pages written like on the subject and a look through the EGFR forums will help give a good understanding of what to expect. http://cancergrace.org/forum/cancer-treatments-symptom-management/egfr-… I don't want to excuse your question by any means I just don't want Dr. West to need to repeat what's been said. I hope you understand that we want to use his time as judiciously as possible.
By all means if you don't find what you're looking for just ask,
Janine
forum moderator
Reply # - December 5, 2013, 08:32 PM
Reply To: ADDING SUPPLEMENTS TO TARCEVA REGIMEN
Most of the side effects with Tarceva emerge within 2-3 weeks of starting the drug. That's when the rash and diarrhea tend to be worst, and things often seem to improve a bit gradually after that. There are some chronic side effects, like nail infections and cracks in the fingertips, which tend to be more problematic with very long-term use, but most people on EGFR inhibitors for long enough to experience these issues are benefiting so much from them that they are very inclined to continue on them over time.
Good luck.
-Dr. West